DESCRIPTION: The roles of reactive oxygen species (ROS), nitric oxide (NO), and cochlear blood flow in cochlear function and in sound-induced hearing loss will be examined with a combination of experimental manipulations and biochemical and physiological measurements. In Aim 1, generation of ROS during and after ischemia will be evaluated by manipulating glutathione levels, measuring NO levels, blocking NO synthesis, and chelating iron (to diminish production of hydroxyl radical). In Aim 2, roles of these factors in sound-induced hearing loss will be evaluated by examining the effects of similar manipulations on short-term and long-term hearing loss after high-level exposure to sound, and by hemodilution to alter blood flow and oxygen delivery. In Aim 3, a newly-discovered trigeminal C-fiber innervation of the cochlear vasculature will be studied by electrical stimulation, observing the effects of on blood flow and cochlear vascular permeability, and by tract-tracing to establish more completely its anatomical path.